Decoding tobacco-related oral cancer ecosystem by integrative approach

项目总结 口腔癌的已知危险因素是吸烟和饮酒以及人类乳头瘤病毒(HPV)感染。 烟草使用和HPV感染之间存在明显的相互作用。吸烟者的吸烟率要高得多 口腔HPV持续感染是发展为口腔癌的重要危险因素。患有烟草的患者- 相关的口腔癌预后较差。除了烟草对基因组DNA造成的明显损害外， 暴露在香烟烟雾中也会显著影响免疫系统。最近，免疫疗法已经成为 这是口腔癌一个很有前途的治疗选择。细胞程序性死亡-1(PD-1)是临床上常见的 重要的检查点分子，已被证明在与其配体结合时抑制T细胞的功能， PD-L1和PD-L2。Nivolumab和pembrolizumab是两种最有效和最安全的PD-1抑制剂 口腔癌治疗中的数据。虽然持续使用烟草的有害影响一直是 多年来，烟草使用对肿瘤免疫微环境(时间)和 对口腔癌的免疫治疗效果的研究很少。在这项建议中，我们将全面 通过综合多组学方法评估烟草对口腔癌生态系统的影响， 利用口腔癌症特异性时间寻找新的治疗药物，并开发口腔癌症特异性药物 促进烟草相关癌症研究领域的门户网站。

PROJECT SUMMARY Known risk factors for oral cancers are tobacco and alcohol use and human papillomavirus (HPV) infection. There is a clear interaction between tobacco use and HPV infection. Smokers have a significantly higher rate of persistent oral HPV infection which is a significant risk factor to develop oral cancer. Patients with tobacco- related oral cancers have poor prognosis. Apart from the obvious damage tobacco causes to genomic DNA, cigarette smoke exposure also significantly impacts the immune system. Recently immunotherapy has become a promising therapeutic option in oral cancer. Programmed cell death-1 (PD-1) is one of the clinically significant checkpoint molecules that have been shown to suppress T-cell function upon binding to its ligands, PD-L1 and PD-L2. Nivolumab and pembrolizumab are the two PD-1 inhibitors with the most efficacy and safety data in management of oral cancer. While the detrimental effects of continued tobacco use have been established over the years, the effects of tobacco use in the tumor immune microenvironment (TIME) and immunotherapy efficacy in oral cancers are poorly investigated. In this proposal, we will comprehensively evaluate the tobacco-related effects on the oral cancer ecosystem through integrated multi-omics approaches, identify novel therapeutic agents leveraging the oral cancer-specific TIME, and develop an oral cancer specific web portal to advance the field in tobacco-related cancer research.